Richard B RothmanTranslational Pharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland, United States of AmericaPLoS ONE 6:e17735. 2011

Richard B RothmanTranslational Pharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland, United States of AmericaPLoS ONE 6:e17735. 2011

..These observations emphasize the intrinsic limitation of interpreting data from studies conducted in transgenic mice that are not fully characterized...

..Ex vivo autoradiography, however, demonstrated that iv administration of (-)-(1R,3S)-11 produced a dose-dependent, persistent occupation of 5-HT transporter binding sites but not DA transporter sites...

Evidence for the involvement of dopamine transporters in behavioral stimulant effects of modafinil

Structure-activity relationships of substituted N-benzyl piperidines in the GBR series: Synthesis of 4-(2-(bis(4-fluorophenyl)methoxy)ethyl)-1-(2-trifluoromethylbenzyl)piperidine, an allosteric modulator of the serotonin transporter

..The findings suggest that GBR-decanoate, or similar long-acting agents, should be evaluated further as potential treatment adjuncts in the management of METH addiction in humans...

Probes for narcotic receptor mediated phenomena. 43. Synthesis of the ortho-a and para-a, and improved synthesis and optical resolution of the ortho-b and para-b oxide-bridged phenylmorphans: compounds with moderate to low opioid-receptor affinity

..In the present study, we studied the effect of MDMA and 5,7-dihydroxytryptamine (5,7-DHT) on tissue 5-HT levels and the protein expression level of SERT and glial fibrillary acidic protein (GFAP), a validated neurotoxicity marker...

Further exploration of 1-[2-[Bis-(4-fluorophenyl)methoxy]ethyl]piperazine (GBR 12909): role of N-aromatic, N-heteroaromatic, and 3-oxygenated N-phenylpropyl substituents on affinity for the dopamine and serotonin transporter

..In accord with the in vitro data, 6 showed greater potency than 7 in elevating extracellular dopamine levels in a microdialysis assay and in inhibiting cocaine-maintained responding in rhesus monkeys...

..Future efforts should focus on developing new medications that possess the desired therapeutic activity but lack the adverse effects associated with older amphetamine-type anorectics...

Probes for narcotic receptor mediated phenomena. Part 42: synthesis and in vitro pharmacological characterization of the N-methyl and N-phenethyl analogues of the racemic ortho-c and para-c oxide-bridged phenylmorphans

..1 nM) of all of the a- through f-oxide-bridged phenylmorphans. Functional data ([³⁵S]GTP-γ-S) showed that the racemate 12 was more than three times more potent than naloxone as an μ-opioid antagonist...

Probes for narcotic receptor mediated phenomena. 37. Synthesis and opioid binding affinity of the final pair of oxide-bridged phenylmorphans, the ortho- and para-b-isomers and their N-phenethyl analogues, and the synthesis of the N-phenethyl analogues of

..By comparison of the geometry-optimized structures of the newly synthesized compounds, an attempt was made to rationalize their μ-opioid receptor affinity in terms of the spatial position of N-substituents...

..029). Collectively, our findings are consistent with the hypothesis that 5-HT release dampens stimulant effects of amphetamine-type drugs, but further studies are required to address the precise mechanisms underlying this phenomenon...

Noradrenergic and dopaminergic effects of (+)-amphetamine-like stimulants in the baboon Papio anubis

..Viewed collectively, the present data indicate that typical clinical doses of phentermine and (+/-)-ephedrine may not release central DA in humans, a hypothesis that should ultimately be tested in controlled clinical studies...

Dopamine transport inhibitors based on GBR12909 and benztropine as potential medications to treat cocaine addiction

..Our data suggest that GBR-decanoate, or similar agents, may be useful adjuncts in treating methamphetamine dependence. This therapeutic strategy would be especially useful for noncompliant patient populations...

..Release of NE and DA evoked by (+)-norfenfluramine is at least partly mediated via NE transporters. Our results emphasize the potential involvement of noradrenergic mechanisms in the actions of fenfluramines...

..Viewed collectively, it seems possible to develop new medications that selectively release 5-HT without the adverse effects of PPH, VHD or neurotoxicity. Such agents may have utility in treating a variety of psychiatric disorders...

..The results demonstrated that anti-CART peptide IgG up-regulates mu and 5-HT(2A) receptor in the hippocampus and caudate We conclude that CART peptides in the cerebrospinal fluid may exert regulatory effects in the brain...

Effects of dose and route of administration on pharmacokinetics of (+ or -)-3,4-methylenedioxymethamphetamine in the rat

..Future medications discovery efforts should focus on identifying new compounds which possess the equipotent substrate activity at DAT and SERT, but which lack the adverse effects of stimulants developed decades ago...

Locomotor stimulation produced by 3,4-methylenedioxymethamphetamine (MDMA) is correlated with dialysate levels of serotonin and dopamine in rat brain

..0001) and with dialysate DA in accumbens and striatum (P<0.001-0.0001). These data support previous work and suggest the complex spectrum of behaviors produced by MDMA involves 5-HT and DA in a region- and modality-specific manner...

..Among the compounds studied, 4-[(diphenylmethyl)amino]-2-phenylquinazoline (4 g) was identified as a novel partial inhibitor of [(125)I]RTI-55 binding to the dopamine transporter and a partial inhibitor of [(3)H]dopamine uptake...

..Here, we report the semisynthesis of neoclerodane diterpenes and their structure-affinity relationships at opioid receptors. This work will allow the further development of novel opioid receptor ligands...

..In addition, a procedure has been found to remove the furan skeleton completely. Biological results indicate that replacement of the furan ring with an N-sulfonylpyrrole leads to reduced affinity and efficacy at kappa opioid receptors...

Synthetic studies of neoclerodane diterpenes from Salvia divinorum: exploration of the 1-position